Intestinal epithelial cells are able to produce soluble mediators that initiate or amplify inflammatory events in the intestinal mucosa. Interleukin (IL) -8 is suggested to be a cytokine playing a major role during the acute and chronic processes in inflammatory bowel disease (IBD). TH-2 cytokines have been described as down-regulating the inflammatory response. We analyzed the effects of IL-10, IL-13, and IL-4 on IL-8 secretion in intestinal epithelial cells. The human colonic epithelial cell line Caco-2 and freshly isolated intestinal epithelial cells were used. Cells were stimulated with IL-1beta after treatment with TH-2 cytokines. Levels of IL-8 were determined by employing enzyme-linked immunosorbent assay (ELISA). Stimulation with IL-1beta results in a time-dependent IL-8 secretion. The addition of IL-4 and IL-13, but not IL-10, to activated epithelial cells resulted in a strong decrease in IL-8 secretion. Maximal inhibition required that TH-2 cytokines be added up to 60 min before or simultaneous with stimulatory agents. We present novel findings that IL-4 and IL-13 strongly down-regulate IL-8 secretion from intestinal epithelial cells. A microenvironment containing high concentrations of IL-4 and IL-13 may alter the recruitment of immune cells to enterocytes at least partly by inhibiting IL-8 production. This inhibition might diminish the severity of the intestinal inflammatory response and, thus reduce clinical disease activity.